Various pharmaceutical agents are used in a drug therapy. Some of these agents become positive ions (cations) under biological conditions. Recently, a study of a transporter (transport protein), which exists in a cell membrane and contributes to migration of a pharmaceutical agent to a tissue, absorption thereof, renal excretion thereof and biliary excretion thereof by transporting the pharmaceutical agent actively, has been significantly advanced. Among the transporters, an organic cation transporter (OCT) is important to transport a cationic pharmaceutical agent.
Recent studies have revealed that an OCT3 exists not only in the placenta, but also in the kidneys, the small intestine, the lungs, the heart, and the brain.
A nucleoside derivative, a quinoline derivative, and a compound having a tricyclic structure have been reported as OCT3 activity inhibitors. However, it is difficult to use these compounds as drugs because of side effects etc. thereof. In addition, a guanidine derivative has been reported as the OCT3 activity inhibitor (Non Patent Literature 1 described below). However, it has been reported that IC50s of famotidine and cimetidine (histamine H2 receptor antagonists) are 20 μM and 240 μM, respectively, and that IC50s of ramosetron and granisetron (setron-based compounds) are both 100 μM or less.
Meanwhile, WO 2005/084707 A (Patent Literature 1) discloses a therapeutic agent for mental disorder, containing a substance suppressing expression of an organic cation transporter OCT3 gene as an active component. US 2007/0136828 (Patent Literature 2) discloses a therapeutic agent for depression by inhibiting a function of the OCT3, containing an antisense nucleic acid of the OCT3 gene. WO 2009/134877 A (Patent Literature 3) discloses a therapeutic agent for depression by inhibiting a function of the OCT3, containing an alkylamine-catechol derivative, a quinoline derivative, and a bis-quinoline derivative as active components. WO 2001/93863 A (Patent Literature 4) discloses a therapeutic agent for depression and symptoms suggesting depression, containing famotidine as an active component. U.S. Pat. No. 6,403,645 (Patent Literature 5) discloses a therapeutic agent for depression, containing a transporter Uptake2 (OCT and PMAT) inhibitor as an active component.
According to these literatures, it has been established that depression and symptoms suggesting depression can be treated by inhibiting the organic cation transporter OCT3.
These pharmaceutical agents are disadvantageous in view of intracerebral transferability and nephrotoxicity. Therefore, development of a novel OCT3 activity inhibitor having a completely different basic structure has been desired. In addition, development of an OCT3 detection agent has been desired.
A medicine containing an imidazo[1,2-a]pyridine derivative as an active component is known. For example, Zolpidem (registered trademark) is a therapeutic agent for insomnia, which acts on a ω1-type GABAA receptor. Alpidem (registered trademark) is an anxiolytic drug which acts on a peripheral benzodiazepine receptor. Zolimidin (registered trademark) is an antiulcer drug. Olprinone (registered trademark) is a therapeutic agent for acute heart failure, which inhibits PDE3.